Probing Host‐Guest Inclusion Complex of DHP with β‐CD in Augmenting Bioavailability to Boost Biochemical Applications Optimized by Physicochemical and Molecular Docking

Abstract

This research aims to develop the inclusion complex of 2, 4‐diamino‐6‐hydroxypyrimidine (DHP) with β‐cyclodextrin (β‐CD) using an inclusion process, and to investigate the effect of inclusion on the photo stability and bioactivity of DHP. The formation of DHP‐β‐CD inclusion complex has been examined by means of physicochemical as well as spectroscopic techniques (1H NMR, FT‐IR, PXRD and SEM) suggesting the successful inclusion of the DHP molecule into the β‐CD cavity. The 1 : 1 stoichiometry of the inclusion complex was validated through Job's plot. β‐CD displayed a fairly strong affinity (Ka =889.67 M−1) for DHP, indicating that the binding process is thermodynamically feasible. A molecular docking study speculated the most preferred orientation of DHP molecule within the binding pocket of β‐CD cavity. The photostability of DHP was found to improve on complexation with β‐CD. In vitro antibacterial activity test demonstrated that the DHP‐β‐CD inclusion complex displayed better activity than pure DHP. DHP‐β‐CD inclusion complex (IC50 =240.04 μM) also exhibited relatively significant in vitro cytotoxic activity than pure DHP towards the human kidney cancer cell line (ACHN). These results reveals that the inclusion of DHP using β‐CD could lead to stabilization of DHP and efficient display of its bioactivity.